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Marsha Regenstein, et. al.
Marsha Regenstein, Ellie Andres, Dylan Nelson, Stephanie David, Ruth Lopert and Richard Katz, Medication Information for Patients with Limited English Proficiency: Lessons from the European Union, 40 Journal of Law, Medicine & Ethics 1025 (Winter 2012) (66 Footnotes)
Access to clear and concise medication information is essential to support safe and effective use of prescription drugs. Patient misunderstanding of medication information is a common reason for non-adherence to medication regimens and a leading cause of outpatient medication errors and adverse drug events in the U.S. Medication errors are the most common source of risk to patient safety, leading to poor health outcomes, hospitalizations, and deaths. Over half a million adverse drug events occur in the outpatient setting each year at a cost of approximately $1 billion annually.
Nearly half of adults in the U.S. experience difficulty understanding and acting upon health information. Even individuals with high levels of general literacy may find medication information difficult to understand or use. The risk of misunderstanding medication information is compounded for patients with limited English proficiency (LEP) who may not have access to this information in their own language. Several studies underscore the particular challenges that misunderstanding of medication information creates for patients with LEP and demonstrate that language barriers may be a significant cause of medication errors. Examples of patients with LEP who have experienced medication errors as a result of language barriers abound, such as the common and treacherous example of “once daily” in English being easily confused with “eleven times” in Spanish.
Given the high incidence, significant risks, and substantial costs of medication errors, the Institute of Medicine has dedicated considerable attention to the issue as a quality concern. For medicines to be effective, patients must understand and comply with dosage, timing, and other instructions--an expectation that cannot be met if the necessary information is not understandable to the patient. Likewise, the safe use of medicines requires patients to understand information about side effects, warnings, contraindications, and interactions with other medications or foods. For reasons of equity, the language spoken by the patient should not serve as a barrier to accessible and accurate medication information.
In its 2006 report, Preventing Medication Errors, the Institute of Medicine drew attention to the issue of language barriers related to medication information and offered recommendations for improvements, including necessary accommodations for patients with LEP, such as translations of prescription labels and information leaflets. Similarly the Joint Commission, the National Quality Forum, and the National Committee on Quality Assurance each have standards that include broad requirements or recommendations for translating essential documents.
The United States lags behind the European Union (E.U.) in terms of practices related to the delivery of medication information in multiple languages. Since 1995, the centralized drug approval procedure in the E.U. has required pharmaceutical manufacturers to make medication information available in the official languages of E.U. member states. U.S. regulatory frameworks do not impose any obligations regarding the translation of medication information into multiple languages, and consequently, this information is rarely available in the U.S. in languages other than English.
This paper describes regulations and practices related to the delivery of medication information to U.S. consumers, and examines practices in the E.U. that may serve as a model for future U.S. policy efforts to improve the quality and availability of medication information for individuals with limited English proficiency.
The Need for Medication Information in the Patient's Language
More than one in five people living in the U.S. speak a language other than English at home. A large and growing group of individuals, numbering more than 25 million in 2011, have LEP and consequently face enormous challenges when communicating with health professionals about medication use. Compared to English-speaking individuals, persons with LEP are more likely to experience medication errors and less likely to understand medication and dosing information or adhere to recommended medication regimens.
Title VI of the Civil Rights Act of 1964, which prohibits discrimination based on national origin, has been widely interpreted as prohibiting discrimination against LEP persons. Entities receiving federal funding, including pharmacies, must provide meaningful access to individuals with LEP. In addition, all states have laws supporting the provision of language services during patient counseling, the distribution of written information, or both. However, oversight of the health care industry's compliance with these rules is extremely limited; federal regulation related to medication information does not require pharmacies or pharmaceutical companies to make such information available in any language other than English.
Unfortunately, medication information from pharmaceutical manufacturers is rarely available in languages other than English. Also, despite poor outcomes associated with misunderstanding medication information, few pharmacies translate prescription instructions, print non-English prescription labels, prepare non-English information packets, or communicate with consumers in languages other than English. Many pharmacies lack access to translation software, telephone interpretation services, or appropriately skilled personnel with fluency in other languages. While chain pharmacies and pharmacies with large LEP patient populations are more likely to have some capacity to translate prescription labels either verbally or in print, researchers have found that translation practices are often inconsistent and potentially hazardous, risking perpetuating health disparities among LEP patients.
Medication Information in the U.S.
In the U.S., there are a number of ways by which medication information is presented and distributed to patients. When filling prescriptions at a pharmacy, individuals may receive four types of patient medication information: the prescription container label, medication guide, package insert, and consumer medication information (see Table 1 omitted).
Prescription Container Labels
The prescription container label is the primary source of medication information used by patients because it is affixed to the medication container and is therefore less likely to be disposed of or lost. All states have laws regulating container labels. Most state provisions mirror federal Food and Drug Administration (FDA) standards for the content of container labels and require that the label include the name of the drug, patient, physician and pharmacy, as well as the “Rx number” and refill status. The label also contains dosing and administration instructions as provided by the patient's physician, as well as auxiliary warning statements, often presented in a variety of colors with different pictures (e.g., may cause drowsiness; avoid alcohol while taking this medication).
Efforts to ensure language access related to prescription drugs tend to target the prescription container label generated by the pharmacy. In September 2009, New York City became the first locality in the U.S. to require translation services in certain pharmacies. Among other requirements, New York City's law mandates translation of container labels into the top seven languages spoken by LEP persons in the city. New York City's statute followed a civil rights complaint brought against several chain pharmacies in New York State. As part of the settlement, the chain stores involved were required to translate prescription labels into eleven languages by May 2010. On March 30, 2012, New York State approved legislation essentially expanding the New York City translation requirement to benefit individuals with LEP throughout the state. Additionally, recent legislation in California requires the Board of Pharmacy to publish translations of prescription label instructions in at least five languages other than English on its website, in order to facilitate the use of translations in California pharmacies.
Medication Guides
In 1998, the FDA issued regulations requiring drug manufacturers to provide consumers with medication guides (Med Guides), 1-2 page paper handouts for a limited number of drugs that the FDA considers to “pose a serious and significant public health concern.” The guides are currently available for approximately 250 different drugs and are intended to help patients avoid serious adverse events. Med Guides are developed by the pharmaceutical manufacturer and are subject to FDA approval. A 2008 evaluation of medication information commissioned by the FDA found that very few patients received Med Guides and many pharmacies were not aware of their responsibility to provide them to patients.
While the FDA requires that Med Guides be written in English, in non-technical, understandable language without promotional tone or content, it does not require them to be translated into languages other than English. At the time the regulation was issued, the FDA acknowledged public concerns about the availability of Med Guides in Spanish and other languages and encouraged manufacturers to develop Med Guides in languages other than English. However, translated Med Guides are not subject to FDA approval and the agency has asserted that it will not review versions of labeling in languages other than English, whether as part of a new or supplemental drug application.
Patient Package Inserts
In addition to medication guides, the FDA also maintains regulatory oversight for consumer-directed information for oral contraceptives and certain products containing estrogens. This information is in the form of a patient package insert (PPI), typically presented as a folded leaflet inside the unit-of-use packaging. Each PPI is developed by the drug's manufacturer, who may also voluntarily provide PPIs for other types of drugs. Although PPI regulations do not specifically state whether the information must appear in English or any other language, it is presumed to be required in English since the information is necessary for FDA approval.
Consumer Medication Information
Consumer medication information (CMI) includes information on the medication's purpose, indications and contraindications, side effects, and warnings; it is often stapled to the outside or placed inside the pharmacy-provided prescription bag. Although pharmacies are not required to provide CMI to consumers, most do so voluntarily, providing information that they either develop internally or purchase through third-party vendors. Pharmacy practices vary, with some pharmacies providing CMI documents only for new prescriptions and others including them routinely with all prescription medications. Unlike Med Guides and Patient Package Inserts, CMI documents are not reviewed, approved or regulated by the FDA.
Over the past two decades, the value of the CMI as a patient education tool has been called into question, in part because of variability in the quality of the information and lack of clear standards and regulatory oversight governing CMI content and availability. Nevertheless, CMI is one of few sources of medication information in the U.S. that has included some limited discussion of availability in languages other than English.
The European Union: Translation of Medication Information
The E.U. takes a far different approach than the U.S. when it comes to the translation of medication information. The E.U. has incorporated the translation of medication information into its centralized drug approval procedure, requiring translated medication information targeted to consumers in the official languages of the E.U. member states.
In 1995, the E.U. established the European Medicines Evaluation Agency and with it, an opportunity for the pharmaceutical industry to consolidate the drug approval process across E.U. member states. The agency, now known as the European Medicines Agency (EMA), is responsible for evaluating drug approval applications, post-market monitoring and pharmacovigilance, and providing scientific advice to companies developing new drugs. Pharmaceutical companies wishing to market their drugs in E.U. countries can choose to use the EMA's centralized drug approval procedure or submit drug approval applications directly to one or more member states. The benefit of using the centralized procedure is that, if successful, the drug approval extends across all E.U. countries. The downside is that the centralized procedure contains requirements that are not necessarily included in an individual country's application process. The centralized procedure must be used for certain drug classes; for example, certain biologicals and medicines for the treatment of AIDS, cancer, diabetes, and orphan medical products can only be approved for sale in the E.U. through the centralized procedure.
Drug Approval Process under the Centralized Procedure
The EMA has very specific requirements concerning the development of medication information as part of its marketing approval process. Materials must be prepared in English for the initial review process. If the drug receives preliminary approval (subject to further review and final approval), the medication information must then be translated by the manufacturer into 24 languages and Braille.
The EMA provides oversight for consumer-directed medication information through its Working Group on Quality Review of Documents, which conducts a detailed review of the English-language version of the medication information. In addition to the content, the review covers the style and layout of the information. The Working Group reviews the labeling and package information leaflet and, if satisfactory, the materials are forwarded to representatives of each member state, who in turn conduct their own review of the English-language versions of the medication information. Some additional back and forth discussion during the review process is common between the applicant and the various national and EMA reviewers. A team of medical writers also conducts a review of the documents and submits a final decision regarding approval of the documents as one component of the overall drug application.
EMA decisions to approve medications are conditional upon the applicant's submission of translations of the approved English-version medication information into 24 other languages plus Braille.
Pharmaceutical Labeling Requirements
An important feature of drug packaging in the E.U. (and most of the industrialized world) is that medicines are not generally shipped in bulk for repackaging in pharmacies, but instead are packaged for individual consumers with tablets generally supplied in blister packaging.
The EMA requires pharmaceutical companies to provide information to consumers on two areas of the drug's package as well as via a leaflet included with or inside the package (see Table l). These are referred to as the outer packaging, the inner packaging, and the patient information leaflet.
Outer Packaging
The box which holds the blister pack, bottle, or other direct container of the drug constitutes the outer packaging. The outer packaging must contain the product's name, strength, active substances, method of administration, and any necessary warning statements (e.g., keep out of reach of children). The outer packaging must also include the expiration date, the production batch number, storage instructions, disposal instructions for unused doses, as well as the name and contact information of the manufacturer. Individual member states may require additional information on outer packaging, such as information regarding the cost of the drug and how it can be accessed through various social service agencies.
Inner Packaging
The inner packaging is the container that directly encloses the pharmaceutical. Inner packaging is required to display the same information as the outer packaging. The majority of prescriptions in the E.U. are distributed through blister packs, which provide too little space to include all of the required information and still meet guidelines for legibility and comprehensibility. For this reason, most inner packaging qualifies for an exemption from this requirement. At a minimum, blister packs must contain the name of the drug and manufacturer, the expiration date and the batch number.
Patient Information Leaflet
The Patient Information Leaflet is provided to consumers separately with each prescription purchased at the pharmacy or included within the outer packaging. It is the most comprehensive information provided with each drug. In addition to many of the items required on the outer packaging, the patient information leaflet includes the approved indications of the drug, contraindications, interactions with drugs, food, or other substances, drug administration instructions, reported side effects, and a detailed list of drug components. Individual member states may require additional information, commonly referred to as a “blue box,” that provides country-specific information such as price, health insurance coverage details, and availability through social service agencies.
The patient information leaflet must be written specifically for and reviewed by consumers. As part of the marketing approval process, the EMA requires manufacturers to undertake targeted patient reviews of the English-language versions of the leaflets to make sure that they are legible, clear, and easily understood. Generally, this takes place through consumer testing of patients' understanding of important components of a draft version of the leaflet. The results of these consumer tests must be included in the initial marketing approval application to the EMA and are taken into account when revising the materials. Consumers are targeted based on the intended users of the drug; for example, leaflets on diabetes medications must be tested by consumers with diabetes.
Translation Process
The outer packaging and patient information leaflet must be available in the official language or, in the case of countries like Belgium that have multiple official languages, the languages of each of the E.U. member states in which a medication is sold. In countries with two official languages, both languages must appear on all medication labels. Additionally, the name of the drug must be printed in Braille on both the outer and inner packaging, and the entire patient information leaflet must be available in Braille on request.
The window for completing the required translations is remarkably short. Pharmaceutical manufacturers must submit translations of their English-language versions of packaging and patient information, in 24 other languages plus Braille, to the EMA no longer than five days after the initial application has been granted conditional approval. In practice, companies begin the translation process long before the English-language versions have received conditional approval. After they have been submitted by applicant companies, the EMA forwards the translations to regulatory agencies in member states for review and comment. France and Germany, for example, review the French and German materials to be used in member states where these languages are spoken. The review process for the translated documents is also quite rapid. Designated E.U. member state pharmaceutical regulatory agencies must complete their language-specific reviews within two weeks of receiving the translated medical information, at which point they provide comments and questions for the applicant. Guidance from the European Commission on requirements for translation of the patient information leaflet states that the translations should be “faithful [to the user-tested English-version,] allowing for regional translation flexibility, whilst maintaining the same core meaning,” rather than a literal translation of the English words, which could be confusing or change the meaning of the original.
The short (five-day) turnaround time between initial approval and submission of translations is considered very onerous by the pharmaceutical industry. The two-week translation review period at the country drug agency level is also considered inadequate. Translation review duties are often in addition to the regular demands of the jobs held by reviewers and deadlines are often missed, delaying the application review. Revised translations indicating how comments by reviewers have been addressed are submitted along with the full drug application.
Pharmaceutical companies use both staff and contractors to prepare translations. Information on the cost of the translation process to manufacturers is proprietary; however, one estimate suggests that the resources necessary to complete the translations correspond to two full time equivalent employees. Despite the burden associated with the translation process, pharmaceutical manufacturers routinely use the centralized procedure to gain access to a drug market of over half a billion people. The efficiencies associated with the centralized procedure greatly offset the relatively small costs associated with translations.
Discussion
Pharmaceutical regulatory policies in the U.S. and E.U. have addressed the need for information to support consumers' safe use of medications, with the E.U. taking explicit steps to mandate the availability of the information in the official languages of its member states. Most attention in the U.S. has focused on the dispensing label to convey information to patients about the medication they have been prescribed and their treatment regimen. Other forms of consumer-directed information (patient package insert and medication guides) are required by the FDA, although one of the most common forms of information--the CMI that is usually stapled to the prescription at the point of purchase--is unregulated and highly variable. As noted above, the FDA does not require medication information to be available in any language other than English, despite an acknowledged need for the information, a rapidly growing LEP population, and an appreciation of the cost to patients and the health system from medication errors.
The drug approval process in the E.U. provides a clear example of how readily medication information can be made available in multiple languages. Embedding the development of approximately two dozen translations of medication information in the marketing approval process accomplishes several things. First, pharmaceutical manufacturers have a strong incentive to complete all required translations expeditiously, since drug approval is contingent upon this process and a review of the documents is incorporated into the drug approval timeline. Second, bundling multiple translations into a single requirement means that new member states that participate in the EMA approval process have their official languages automatically included. This eliminates often contentious debates about the appropriate threshold of market penetration of various language groups for translating documents into particular languages. Finally, extremely narrow time windows for submission of translations to the EMA and the review of those translations at the country level support a process that does not substantially delay market entry.
Pharmaceutical manufacturers in the E.U. reportedly find the translation requirements to be burdensome, but they do not complain that they are technologically or organizationally complex. According to representatives from the EMA, companies routinely comply with the translation requirements and are able to submit documents in multiple languages, generally within the scheduled timeframes. Drug applications are often prepared through contractual relationships with translation firms that are familiar with the E.U. requirements related to quality and timeliness. While not without cost, the translations do not appear to add significantly to the cost of preparing an application for marketing approval.
The E.U. experience should lay to rest the notion that the translation of medication information into multiple languages is an impossible or even impractical task. Requiring pharmaceutical companies to prepare translations of medication information in the official languages of the E.U. as part of the drug approval process, according to clearly specified standards and criteria, has resulted in transformational practices that are now taken for granted.
Despite the differences in practices between the E.U. and the U.S., the E.U. example can serve as a model for the U.S. to improve the quality and availability of medication information in LEP patients' own languages. Requirements related to the translation of medication information on the part of manufacturers, for information already regulated by the FDA, could be incorporated into the U.S. drug application process. Uniform translations could be distributed along with medications from manufacturers to pharmacies across the U.S., where they could accompany prescriptions at the point of sale. The proposed process would replicate the information included in E.U. packaging without disrupting the pharmacy's dispensing function.
The focus on the pharmacy and the prescription label holds promise for improvement, but so does an equal spotlight on the drug manufacturers, whose customers make up a much more linguistically diverse group than those of the typical retail drugstore. Many of the pharmaceutical companies responsible for providing translations for the marketing approval process in the E.U. are the same companies selling pharmaceuticals in the U.S., and thus, already have some capacity to provide translations of medication information in many of the languages spoken by LEP persons in the U.S. Combining a requirement for uniform, clear, and understandable medication information in multiple languages at both the pharmacy and pharmaceutical manufacturer levels could substantially advance the safety of medication use among persons with limited English proficiency across the U.S.
Marsha Regenstein, Ph.D., M.C.P.,is a Professor in the Department of Health Policy at the George Washington University School of Public Health and Health Services in Washington, D.C. and served as the Director of Speaking Together: National Language Services Network.
Ellie Andres, M.P.H.,is a Senior Research Associate in the Department of Health Policy at the George Washington University School of Public Health and Health Services.
Dylan Nelsonis a Senior Research Assistant in the Department of Health Policy at the George Washington University School of Public Health and Health Services.
Stephanie David, J.D., M.P.H.,is an Assistant Research Professor in the Department of Health Policy at the George Washington University School of Public Health and Health Services.
Ruth Lopert, B.Sc, B.Med., M.Med.Sc, F.A.F.P.H.M.,is a Visiting Professor in the Department of Health Policy at the George Washington University School of Public Health and Health Services.
Richard Katz, M.D.,is the Bloedorn Professor of Medicine and Director of the Division of Cardiology at the George Washington University Medical Faculty Associates.
